RESCUE OF ERYTHROID DEVELOPMENT IN GENE TARGETED GATA-1- MOUSE EMBRYONIC STEM-CELLS
RESCUE OF ERYTHROID DEVELOPMENT IN GENE TARGETED GATA-1- MOUSE EMBRYONIC STEM-CELLS
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DOI：
10.1038/ng0592-92
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发表时间：
1992-05-01
期刊：
影响因子：
30.8
通讯作者：
ORKIN, SH
中科院分区：
文献类型：
--
作者：
SIMON, MC;PEVNY, L;ORKIN, SH
转录因子加塔-1编码基因的靶向突变可阻断定型（胎肝衍生）红细胞的发育。我们使用体外分化的加塔-1-小鼠胚胎干（ES）细胞，揭示了原始（卵黄囊衍生）红细胞生成过程中对加塔-1的需求，并建立了一个救援试验。我们表明，块发展包括原始的，以及永久的，红细胞，是完整的珠蛋白RNA表达的水平，一个正常的加塔-1基因的引入恢复在体内和体外的发展潜力，有效的救援是依赖于一个假定的自动调节GATA基序在远端启动子。使用体外分化的ES细胞弥补了细胞系中基因功能的常规方法与整个动物中功能缺失突变分析之间的差距。
Development of definitive (fetal liver-derived) red cells is blocked by a targeted mutation in the gene encoding the transcription factor GATA-1. We used in vitro differentiation of GATA-1- mouse embryonic stem (ES) cells to reveal a requirement for GATA-1 during primitive (yolk sac-derived) erythropoiesis and to establish a rescue assay. We show that the block to development includes primitive, as well as definitive, erythroid cells and is complete at the level of globin RNA expression; that the introduction of a normal GATA-1 gene restores developmental potential both in vivo and in vitro; and that efficient rescue is dependent on a putative autoregulatory GATA-motif in the distal promoter. Use of in vitro differentiated ES cells bridges a gap between conventional approaches to gene function in cell lines and analysis of loss of function mutations in the whole animal.